创作:mildbreeze 审核:mildbreeze 08月01日
  • 分析36名环境肠功能障碍(EED)患儿的十二指肠微生物群,鉴定出14个不属于典型肠道病原体的EED核心细菌类群;
  • 这些细菌(某韦荣球菌、某链球菌和Rothia mucilaginosa等)的绝对水平,与患儿生长负相关,与参与免疫炎症应答的十二指肠蛋白(如LCN2)正相关,且在患儿粪便中的含量不同于健康儿童;
  • 和EED核心菌相关的十二指肠蛋白,与血浆REG3A等显著相关;
  • 定植EED十二指肠菌群的部分分离菌(含大部分EED核心菌)可引起小鼠小肠病变。
环境肠功能障碍(EED)是一种小肠疾病,被认为是儿童发育不良的潜在原因,但由于小肠样本难以获取,人们对这种疾病还所知有限。New England Journal of Medicine杂志最新发表了Jeffrey Gordon团队主导的一项研究,对孟加拉80名经活检确诊为EED的营养干预无效的发育不良儿童的血浆和十二指肠蛋白组、十二指肠组织病理,以及其中36名患儿的十二指肠微生物组等进行分析,鉴定出与发育不良相关的14个EED核心十二指肠细菌类群,以及潜在的十二指肠和血浆蛋白标志物。结合悉生小鼠模型,该研究表明这些EED菌群可能通过促进十二指肠炎症应答,参与EED的发生发展,从而导致发育不良。这些发现为调控小肠菌群来治疗EED相关儿童发育不良的干预策略,提供了支持证据。

Duodenal Microbiota in Stunted Undernourished Children with Enteropathy



07-23, Article

Abstract & Authors:展开

BACKGROUND: Environmental enteric dysfunction (EED) is an enigmatic disorder of the small intestine that is postulated to play a role in childhood undernutrition, a pressing global health problem. Defining the incidence of this disorder, its pathophysiological features, and its contribution to impaired linear and ponderal growth has been hampered by the difficulty in directly sampling the small intestinal mucosa and microbial community (microbiota).
METHODS: In this study, among 110 young children (mean age, 18 months) with linear growth stunting who were living in an urban slum in Dhaka, Bangladesh, and had not benefited from a nutritional intervention, we performed endoscopy in 80 children who had biopsy-confirmed EED and available plasma and duodenal samples. We quantified the levels of 4077 plasma proteins and 2619 proteins in duodenal biopsy samples obtained from these children. The levels of bacterial strains in microbiota recovered from duodenal aspirate from each child were determined with the use of culture-independent methods. In addition, we obtained 21 plasma samples and 27 fecal samples from age-matched healthy children living in the same area. Young germ-free mice that had been fed a Bangladeshi diet were colonized with bacterial strains cultured from the duodenal aspirates.
RESULTS: Of the bacterial strains that were obtained from the children, the absolute levels of a shared group of 14 taxa (which are not typically classified as enteropathogens) were negatively correlated with linear growth (length-for-age z score, r=−0.49; P=0.003) and positively correlated with duodenal proteins involved in immunoinflammatory responses. The representation of these 14 duodenal taxa in fecal microbiota was significantly different from that in samples obtained from healthy children (P<0.001 by permutational multivariate analysis of variance). Enteropathy of the small intestine developed in gnotobiotic mice that had been colonized with cultured duodenal strains obtained from children with EED.
CONCLUSIONS: These results provide support for a causal relationship between growth stunting and components of the small intestinal microbiota and enteropathy and offer a rationale for developing therapies that target these microbial contributions to EED. (Funded by the Bill and Melinda Gates Foundation and others; number, NCT02812615. opens in new tab.)

First Authors:
Robert Y Chen,Vanderlene L Kung

Correspondence Authors:
Tahmeed Ahmed,Jeffrey I Gordon

All Authors:
Robert Y Chen,Vanderlene L Kung,Subhasish Das,M Shabab Hossain,Matthew C Hibberd,Janaki Guruge,Mustafa Mahfuz,SM Khodeza Nahar Begum,M Masudur Rahman,Shah Mohammad Fahim,M Amran Gazi,Rashidul Haque,Shafiqul A Sarker,Ramendra N Mazumder,Blanda Di Luccia,Kazi Ahsan,Elizabeth Kennedy,Jesus Santiago-Borges,Dmitry A Rodionov,Semen A Leyn,Andrei L Osterman,Michael J Barratt,Tahmeed Ahmed,Jeffrey I Gordon